"The glomerular lesions of HIV-associated nephropathy (HIVAN) are associated with the expression of HIV-1 in podocytes," explained Dr. Peter J. Nelson and colleagues at Mount Sinai School of Medicine in New York City.

Cyclin-dependent kinase inhibitors reduced HIV expression by podocytes in vitro, Nelson and coauthors found.

The researchers added flavopiridol or roscovitine, which block the activity of cyclin-dependent kinase-9, to cultures of podocytes. Both drugs blocked HIV transcription in these cells, they said.

Roscovitine was more effective at preventing podocyte proliferation than flavopiridol, study data showed. However, flavopiridol had a lower inhibitory concentration than its counterpart, with an IC₅₀ of 25 nM compared with the 3 µM IC₅₀ roscovitine.

Both agents enabled the expression of podocyte differentiation markers, which had been suppressed by HIV gene expression (Suppression of HIV-1 expression by inhibitors of cyclin-dependent kinases promotes differentiation of infected podocytes, J Am Soc Nephrol 2001 Dec;12(12):2827-31.

"These results suggest that inhibition of HIV-1 transcription decreases podocyte proliferation and permits the reexpression of differentiation markers," Nelson and coworkers concluded. "Thus, suppression of HIV-1 transcription by selective cyclin-dependent kinase-9 inhibitors may be a useful therapeutic strategy for the treatment of HIVAN."

The corresponding author for this report is Dr. Peter Nelson, Division of Nephrology, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1243, New York, NY 10029, USA. E-mail: peter.nelson@mssm.edu.

Key points reported in this study include

• Cyclin-dependent kinase inhibitors reduce HIV expression by infected podocytes
  


• Suppression of HIV expression enabled the reexpression of podocyte differentiation markers
  


• These agents may be an effective treatment for HIV associated nephropathy
  

This article was prepared by AIDS Weekly editors from staff and other reports.

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